- The location of the tumor and how far it has spread
- Whether the tumor is hormone receptor-positive or -negative
- Genetic factors
- Tumor size and shape
- Rate of cell division
- Biologic markers
The good news is that women are living longer with breast cancer, and at this time more than 2 million American women are survivors. Survivors must live with the uncertainties of possible recurrent cancer and some risk for complications from the treatment itself.
Recurrences of cancer usually develop within 5 years of treatment. However, 25% of recurrences and half of new cancers in the opposite breast occur after 5 years. One study suggested that the risk factors for a first breast cancer do not necessarily place a woman at any higher risk for recurrence. (Women with a first cancer, however, do have a higher risk for a new cancer in the opposite breast. The outlook for such new cancers is independent from those of the first one.)
Location of the Tumor:
The location of the tumor is a major factor in outlook:
- If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes (is node-negative), the 5-year survival rates with treatment are up to 98%. However, cancer recurs in 9 - 30% of such node-negative cancers. Recurrence is a potentially life-threatening problem, even if the disease relapses locally in the same breast. In one study of DCIS patients with locally invasive recurrence, 8-year mortality rates were only 12%.
- If the lymph nodes contain cancer cells (are node positive) then survival rates fall. If the tumor is larger than 5 cm or there is widespread involvement in the lymph nodes, the cancer is sometimes referred to as locally advanced. In such cases, the survival rate drops to about 75% and below.
- If the cancer has spread to other sites (most often the lung, liver, and bone), the average survival time for patients treated with chemotherapy is 1 - 2 years (with some patients living for many years). New combinations of drugs are improving these averages.
- The location of the tumor within the breast is an important prognostic factor. Tumors that develop toward the outside of the breast tend to be less serious than those that occur more toward the middle of the breast.
Hormone Receptor-Positive or -Negative:
- Breast cancer cells may contain receptors, or binding sites, for hormones like estrogen or progesterone. Cells containing these binding sites are known as hormone receptor-positive cells and if they lack them are called hormone receptor-negative cells.
- Hormone receptor-positive cells grow more slowly than receptor negative cells. Women have a better prognosis if their tumors are receptor-positive because these cells grow more slowly than receptor-negative cells and they have more treatment options. (Hormone receptor-negative tumors can be treated only with chemotherapy.)
The Influence of Genes:
Determining a "genetic signature" for a tumor may prove to be a very powerful predictor of the aggressive nature of a breast cancer. Researchers have focused on 70 genes whose activity patterns may help make such predictions.
The relevance of the inherited BRCA1 or BRCA2 mutations to survival is controversial. Some studies have suggested that these mutations offer a survival advantage, while others suggest that they make no difference or even worsen prognosis. Women with these genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1 mutations tend to develop tumors that are hormone receptor negative, which can behave more aggressively.
Tumor Markers:
Researchers are investigating numerous substances in tumor cells that may indicate whether or not a cancer is likely to spread. Such chemical markers may help doctors determine treatments, and some may even prove to be targets for future drugs. The following are only a few of the more well-researched markers.
HER-2. The HER-2 protein is part of the epidermal growth factor receptor family and is becoming an important marker in breast cancer. It is involved in the growth and spread of breast cancer cells, and about 25 - 30% of patients with breast cancer have high levels of this protein. The presence of HER-2 may suggest aggressive cancer. It is proving to be important in determining treatment choices. For example, women who have HER-2 positive cancers tend to benefit from anthracycline-based chemotherapy.
- Angiogenesis Factors. Angiogenesis is the growth of new blood vessels. High levels of angiogenesis factors indicate that the tumor is developing its own supply of blood vessels, which enable the tumor to send colonies of cancer cells into the blood stream and spread to other parts of the body. Specific angiogenesis factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), may turn out to be important markers for determining treatment and prognosis. The monoclonal antibody bevacizumab (Avastin) targets VEGF. The drug is showing promise in clinical trials for prolonging progression-free survival in women with metastatic breast cancer.
- Others. Many other markers are being investigated, including p53, cathepsin-D, protein c-erbB-2, bcl-2, Ki-67, telomerase, thymidylate synthase, CA 15-3, and carcinogenic embryonic antigen (CEA). The American Society of Clinical Oncology (ASCO) cautions, however, that the value of many of these factors has not yet been confirmed.
Other Factors for Predicting Outlook:
- Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated tumors, which have indistinct margins, are more dangerous than those with well-defined margins.
- Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests measure aspects of cancer cell division and may eventually prove to predict the disease. For example, the mitotic index (MI) is a measurement of the rate at which cells divide. The higher the MI, the more aggressive the cancer. Another test measures cells at a certain phase of their division.
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